Positive selection of type 2 diabetes genotypes - the glycaemic threshold hypothesis.

The high prevalence of deleterious polygenic type 2 diabetes (T2D) is a paradox requiring explanation beyond food excess, inactivity and the obesity resulting from positive energy balance. Historically, hunting-foraging and later agrarian communities often manifested a converse negative energy balance due to nutritional deficit and/or high physical energy demand - both potentially resulting in hypoglycaemia. Since hypoglycaemia impairs both reproductive fitness and cognitive function, it is proposed that that by expressing resistance to hypoglycaemia, T2D phenotypes were subject to positive selection. The insulin resistance present in often-associated atherosclerotic cardiovascular disease, metabolic syndrome and polycystic ovarian disease may also explain their frequent coexistence and current prevalence.

High variability of glycated hemoglobin concentrations in patients with IDDM followed over 9 years. What is the best index of long-term glycemic control?

OBJECTIVE: To determine variability of long-term glycemic control in patients with IDDM. RESEARCH DESIGN AND METHODS: A retrospective analysis of HbA1 among 122 IDDM patients followed over 9 years. RESULTS: Annual group mean HbA1 ranged from 8.4 to 9.3% with large standard deviations (1.7-2.0%), indicating marked variability among individuals. Fluctuations of more than +/- 1% HbA1 occurred in 50% of the patients year to year, and over 9 years the minimum-maximum range was > 3 and > 5% HbA1 in 55 and 11% of patients, respectively. In any one year, 22-43% of patients had HbA1 < 8%, but over 9 years only 3.3% were consistently < 8%. Groups divided according to baseline HbA1 of < 8, 8-10, and > 10% were significantly separated over 9 years by frequency distribution analysis of individual mean HbA1 but were indistinguishable when analyzed by individual HbA1 interquartile range (measure of variability). CONCLUSIONS: High variability of long-term glycemic control is a marked feature of IDDM, the extent of which may be relevant to microvascular risk.

Evaluation of a self-calibrating blood glucose monitor.

A new reflectance blood glucose meter designed for hospital use, the Reflocheck (Boehringer-Mannheim, West Germany), was evaluated. The instrument showed excellent correlation with a routine laboratory method (r = 0.996), and the coefficients of variation at high, medium, and low glucose levels were less than 4%.

Effect of computer-based learning on diabetes knowledge and control.

Two interactive computer-based systems have been evaluated: a teaching program with text and animated graphics and a multiple-choice knowledge-assessment program (KAP) with optional prescriptive feedback. One hundred seventy-four routine-attending insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) patients were allocated to active and control groups to determine the effect of these programs on knowledge and control after a 4- to 6-mo follow-up period. Interactive computer teaching (ICT) resulted in a significant knowledge increment in both IDDM and NIDDM patients (P less than .05), together with a mean fall of 0.8 and 0.7%, respectively, in HbA1c (P less than .05 and P greater than .1), but no changes were observed in respective control groups. The KAP with feedback also produced a significant knowledge increment in both IDDM and NIDDM patients (P less than .05), of similar magnitude to the ICT program, and a mean fall in HbA1c of 1.2 and 1.3%, respectively (P less than .05), with no changes in the corresponding control groups. Even when KAP was used without prescriptive feedback, smaller but significant mean falls in HbA1c of 0.7 and 0.8% (P less than .05) were seen in IDDM and NIDDM patients, respectively, suggesting a motivational effect resulting from program participation.(ABSTRACT TRUNCATED AT 250 WORDS)

Final report of the United States Department of Health and Human Services Secretary's Work Group on pediatric human immunodeficiency virus infection and disease: content and implications.

Human immunodeficiency virus (HIV) disease is increasing rapidly in the ranks of the leading causes of death among children. It is already the ninth leading cause of death among children 1 to 4 years of age and the seventh in young people between the ages of 15 and 24 years. If current trends continue, AIDS can be expected to move into the top five leading causes of death in the pediatric and adolescent age group in the next 3 or 4 years. To address this problem and also to provide focus for the US Department of Health and Human Services activities dealing with pediatric AIDS, an intradepartmental work group was established as a central health and human services component. This was done to ensure the best possible use of federal resources on behalf of children and adolescents with AIDS. Its recommendations are the basis of this report.

Infant mortality increase despite high access to tertiary care: an evolving relationship among infant mortality, health care, and socioeconomic change.

In this study, the determinants of an apparent increase in the infant mortality rate of an urban population with high access to tertiary neonatal care are reviewed. For a 4-year period (1980 to 1983), all infant deaths (n = 422) of the 32,329 births to residents of the City of Boston were analyzed through linked vital statistics data and a review of medical records. A significant increase in the infant mortality rate occurred in 1982 due to increases in three components of the infant mortality rate: the birth rate of very low birth weight infants (less than 1,500 g), the neonatal mortality rate of normal birth weight infants (greater than or equal to 2,500 g), and the mortality rate of infants dying during the postneonatal period (28 to 365 days). These increases were associated with inadequate levels of prenatal care. Although transient, the impact of the observed alterations in these infant mortality rate components was enhanced by a more long-standing phenomenon: the stabilization of mortality rates for low birth weight infants. This stabilization allowed the increases in other component rates to be expressed more fully than in previous years. In this report a mechanism is shown whereby fully regionalized neonatal care ultimately may confer to the infant mortality rate a heightened sensitivity to socioeconomic conditions and levels of adequate prenatal care.

Effects of human growth hormone on the secretion of rat growth hormone.

Human growth hormone (hGH) was administered to chronically cannulated male rats and its effect upon the physiological secretory patterns of rat growth hormone (rGH) and prolactin were observed. In comparison with injected control animals, a reduction in the size of spontaneous secretory bursts of rGH was apparent when hormone concentrations were compared 3-6 h after administration of hGH (136.27 +/- 27.31 (S.E.M.) v. 76.22 +/- 20.98 ng/ml respectively). However, the mean frequency of secretory episodes of rGH was unaltered. It is therefore postulated that endogenous rGH may modulate the amplitude but not the rhythmicity of secretory episodes of rGH.

Hyperinsulinaemic hypoglycaemia due to chlorpropamide-induced nesidioblastosis.

A 25 year old woman suffering from recurrent attacks of hypoglycaemia underwent a laparotomy for suspected insulinoma. No tumour was found, but histology showed islet cell hyperplasia and nesidioblastosis. Although these changes have been reported as a cause of hypoglycaemia in infants, they are only rarely the cause of hypoglycaemia in adults; in the present case they were found to be the result of covert sulphonylurea administration. The fact that sulphonylureas can cause nesidioblastosis is not well recognised by either physicians or pathologists and it should be considered before "cryptogenic nesidioblastosis" is deemed the cause of hypoglycaemia in adults.

Hereditary angioedema and thyroid autoimmunity.

Sera from 91 patients with hereditary angioedema were screened for thyroid antibodies. The results for the 77 patients more than 17 years old were compared with previously published data for the prevalence of thyroid disease in a large community (Whickham). Of the female patients with hereditary angioedema, the prevalence of thyroglobulin antibodies (TGA) was 14.0%, higher than the expected 3% (p less than 0.001). The prevalence of thyroid microsomal antibodies (TMA) was 20%, also higher than the expected 7.6% (p less than 0.01). The age distributions of the females in both groups differed: in the group with hereditary angioedema there was a greater proportion of younger patients which should have resulted in a lower prevalence of thyroid antibodies. Adjusting for related patients with hereditary angioedema, there was still an increased prevalence of TGA (p less than 0.01) and TMA (p less than 0.01).

Policies towards pregnancy and addiction. Sticks without carrots.

Throughout this century in the United States, tension has existed between those who believe drug abuse is best combatted through the criminal justice system and those who emphasize a medical/public health model of prevention and treatment. In the last decade this debate has centered around the person of the pregnant addict. The former have construed her addiction as willful harm to the fetus punishable on criminal and child abuse grounds. The latter have countered that pregnancy is a moment of increased motivation for treatment and focused on expansion and improvement of treatment options. Both managed care and welfare reform have exacerbated conditions between these opposing policy approaches. The addicted woman is increasingly caught between policies that punish her drug use without options for overcoming addiction.

Maternal and infant health: effects of moderate reductions in postpartum length of stay.

BACKGROUND: The Newborns' and Mothers' Health Protection Act of 1996 prohibits payers from restricting "benefits for any hospital length of stay in connection with childbirth for the mother or newborn child, following a normal vaginal delivery, to less than 48 hours." The law recognizes the basic right of women and physicians to make decisions about aptness of discharge timing. OBJECTIVE: To provide data as a basis for decisions about aptness of discharge timing by studying the effect of voluntary, moderate reductions in length of postpartum hospital stay on an array of maternal and infant health outcomes. DESIGN: A prospective cohort study. Patients were surveyed by telephone at 3 and 8 weeks postpartum. SETTING: A teaching hospital where 38% of the patients are in a managed care health plan with a noncompulsory reduced stay program offering enhanced prepartum and postpartum services, including home visits. PATIENTS: Consecutive mothers discharged after vaginal delivery during a 3-month period. MAIN OUTCOME MEASURES: The outcomes were health services use within 21 days, breast-feeding, depression, sense of competence, and satisfaction with care. Multivariate analyses adjusted for sociodemographic factors, payer status, services, and social support. RESULTS: Of 1364 eligible patients, 1200 (88%) were surveyed at 3 weeks; of these 1200, 1015 (85%) were resurveyed at 8 weeks. The mean length of stay was 41.9 hours (SD, 12.2 hours). Of patients going home in 30 hours or less, 60.8% belonged to a managed care health plan. The length of stay was not related to the outcomes, except that women hospitalized shorter than 48 hours had more emergency department visits than those staying 40 to 48 hours (adjusted odds ratio, 5.78; 95% confidence interval, 1.19-28.05). CONCLUSIONS: When adequate postpartum outpatient care is accessible, a moderately shorter length of postpartum stay after an uncomplicated vaginal delivery had no adverse effect on an array of outcomes. Researchers and policy makers should seek to better define the content of postpartum services necessary for achieving optimal outcomes for women and newborns; funding should be available to provide such services, regardless of the setting in which they are provided.

Racial disparities in outcomes of military and civilian births in California.

OBJECTIVE: To examine racial disparities in prenatal care utilization, birth weight, and fetal and neonatal mortality in a population for whom financial barriers to health care services are minimal. STUDY-DESIGN: Using linked birth, fetal death, and infant death certificate files, we examined prenatal care utilization, birth weight distribution, and fetal and neonatal mortality rates for all white and black births occurring in military hospitals in California from January 1, 1981, to December 31, 1985. These patterns were compared with the experience of their civilian counterparts during the same time period. RESULTS: Black mothers had higher percentages of births occurring in teenaged and unmarried mothers than did white mothers in military and civilian populations. First-trimester prenatal care initiation was lower for blacks in the military (relative risk, 0.79; 95% confidence interval, 0.75-0.82) and civilian (relative risk, 0.51; 95% confidence interval, 0.50-0.52) populations. However, the scale of the disparity in prenatal care utilization was significantly smaller (P < .001) in the military group. Rates of low birth weight and fetal and neonatal mortality among blacks were elevated in the military and civilian groups. However, the racial disparity in low birth weight was significantly smaller in the military group (P < .01 and P < .001, respectively). CONCLUSIONS: In populations with decreased financial barriers to health care, racial disparities in prenatal care use and low birth weight were reduced. However, the persistence of significant disparities suggests that more comprehensive strategies will be required to ensure equity in birth and neonatal outcome.

Fertility therapy and the risk of very low birth weight.

OBJECTIVE: To test the hypothesis of an association between maternal infertility therapy and the risk of very low birth weight (VLBW), defined as birth weight less than 1500 g, independent of the risk of multiple births, and to estimate the contribution of infertility therapy to the national incidence of VLBW. METHODS: The National Maternal and Infant Health Survey conducted in 1988 was used to develop statistics describing outcomes among this birth cohort and to construct logistic regression models evaluating fertility therapy as an independent risk factor for VLBW. RESULTS: An estimated 10.1% of live births and 18.2% of VLBW births nationally were associated with either maternal subfertility or infertility therapy (6.8% and 11.4%, respectively). The risk of VLBW among women concerned with subfertility (i.e., receiving diagnostic testing or advice on timing intercourse) was 1.4 (95% confidence interval [CI] 1.1, 1.9), whereas that for women undergoing therapeutic interventions (ie, ovarian stimulation, surgery, in vitro fertilization, or artificial insemination) was 2.6 (95% CI 2.1, 3.2). Accounting for effects of multiple gestation, maternal age, and a history of miscarriage, the odds ratios for the concerned and therapy groups were 1.5 (95% CI 1.1, 1.9) and 2.0 (95% CI 1.5, 2.5), respectively. Black women were less likely to use fertility therapy but more likely to experience a therapy-related VLBW. CONCLUSION: Fertility therapy is associated with an important portion of all VLBW and with an elevated risk of VLBW, related only in part to an increased risk of multiple gestations. Women expressing concern about subfertility but not receiving therapy are also at increased risk of VLBW, suggesting that a history of infertility may mediate part of the risk associated with fertility therapy.

The impact of extreme prematurity and congenital anomalies on the interpretation of international comparisons of infant mortality.

OBJECTIVE: To identify the potential impact that different definitions of live births and practice patterns have on infant mortality rates in England and Wales, France, Japan, and the United States. METHODS: United States data were obtained from the 1986 linked national birth-infant death cohort, and those for the other countries came from either published sources or directly from the Ministries of Health. RESULTS: In 1986 in the United States, infants weighing less than 1 kg accounted for 36% of deaths (32% white and 46% black); 32% resulted from fatal congenital anomalies. These rates were much higher in both categories than in England and Wales in 1990 (24 and 22%, respectively), France in 1990 (15 and 25%, respectively), and Japan in 1991 (9% for infants weighing less than 1 kg, percentage of fatal congenital anomalies unknown). These cases are more likely to be excluded from infant mortality statistics in their countries than in the United States. CONCLUSIONS: In 1990, the United States infant mortality rate was 9.2 per 1000 live births, ranking the United States 19th internationally. However, infant mortality provides a poor comparative measure of reproductive outcome because there are enormous regional and international differences in clinical practices and in the way live births are classified. Future international and state comparisons of reproductive health should standardize the definition of a live birth and fatal congenital anomaly, and use weight-specific fetal-infant mortality ratios and perinatal statistics.

Confronting racial disparities in infant mortality: reconciling science and politics.

The public debate surrounding disparities in infant mortality has resulted from a profound failure to seek a common wisdom. Because of its essential social roots, infant mortality will always remain the province of fundamental ideological and political conflict. However, without a more integrated analytic approach, progress in reducing disparate infant mortality will remain limited by internecine struggles for disciplinary purview and false claims of societal relevance. For in the end, the struggle to address disparate infant mortality will be advanced best by integrated technical and political strategies that recognize that the pursuits of efficacy and justice are inextricably linked.

Activation of erythrocyte aldose reductase in man in response to glycaemic challenge.

Flux via the polyol pathway, which comprises the enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH), has been implicated in the debilitating complications of diabetes. Previous studies in this laboratory have indicated that erythrocyte AR activities are increased (by 72%) in insulin-dependent diabetic patients. To investigate the mechanism underlying this activation, the response of AR activity to oral glucose challenge was investigated in eight overnight-fasted human volunteers. Glucose consumption led to a transient activation (by 76%: P less than 0.01) of erythrocyte AR, which paralleled the rise and subsequent fall in blood glucose concentrations. It is concluded that erythrocyte AR activity is acutely modulated in response to hyperglycaemia by an as yet unknown mechanism.

Restriction fragment length polymorphisms of the human aldose reductase gene: a preliminary report.

Abnormal metabolism through the polyol pathway during episodes of hyperglycaemia is implicated in the development of the chronic complications of diabetes. Since aldose reductase is the first and ratelimiting enzyme of the polyol pathway, it is predicted that restriction fragment length polymorphisms at the aldose reductase gene locus may influence catalytic activity and determine individual susceptibility to the diabetic complications. This paper reports the existence of EcoRI and TaqI restriction fragment length polymorphisms at the human aldose reductase locus.

Comparison of paired short Synacthen and insulin tolerance tests soon after pituitary surgery.

The cortisol responses to hypoglycaemia (insulin tolerance test, ITT) and tetracosactrin (short Synacthen test, SST) were compared after hypophysectomy to evaluate the SST for the assessment of hypothalamo-pituitary-adrenocortical (HPA) axis function in the immediate post-operative period. In 12 patients who were tested a mean of 21 months postoperatively (range 1-96) peak plasma cortisol in the SST correlated with that in the ITT (r = 0.90). Correlation was also seen in 12 patients tested a mean of 9 days (range 4-18) after hypophysectomy (r = 0.73). Basal-peak cortisol increments did not correlate. The peak plasma cortisol response in each test was classified by comparison with a reference value of 550 nmol/L. On this basis there was a notable discrepancy between the ITT and SST results in only one patient who was tested 4 days after hypophysectomy. The close correlation between ITT and SST responses after pituitary surgery extends into the immediate post operative period and indicates that the latter test can be used to screen HPA axis function at this time.

Investigation of hirsutism: testosterone is not enough.

In a consecutive series of 41 hirsute women clinically classified as benign androgen excess, only 34% were found to have elevated plasma 'total' testosterone (T), 22% having subnormal sex hormone binding globulin (SHBG). When expressed as the ratio T/SHBG ('free androgen index'), 85% of the patients had values above the normal range. It is concluded that this index is more reliable than total testosterone in assessing androgen status in female patients.

Poverty and child health.

Poverty is now more heavily concentrated in children than at any other time in U.S. history. Poverty's influence on child health is pervasive and creates a variety of clinical challenges. This discussion reviews the clinical expression of poverty in childhood and assesses our clinical and political capacity to reduce its tragic impact.